Synthesis of 1,3,5-trisubstituted 1H-1,2,4-triazoles containing hetaryl fragments

Article abstract of DOI:10.1023/A:1025638910987

N¹-Phenyl- and N¹-(3,5-dichloro-2-pyridyl) amidrazones have been synthesized by the reaction of imino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine. Acylation of the products with acid chlorides leads to 1-phenyl- and 1-(3,5-dichloro-2-pyridyl)-3-hetaryl-5-R²-1H-1,2,4-triazoles. Compounds of this type are also formed by the condensation of N-acylimino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine.

Full text of DOI:10.1023/A:1025638910987

Chemistry of Heterocyclic Compounds, Vol. 39, No. 6, 2003
SYNTHESIS OF 1,3,5-TRISUBSTITUTED
1H-1,2,4-TRIAZOLES CONTAINING
HETARYL FRAGMENTS
V. I. Kelarev, M. A. Silin, K. I. Kobrakov2, I. I. Rybina2, and V. K. Korolev2
N1-Phenyl- and N1-(3,5-dichloro-2-pyridyl)amidrazones have been synthesized by the reaction of imino
esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine. Acylation of the products
with acid chlorides leads to 1-phenyl- and 1-(3,5-dichloro-2-pyridyl)-3-hetaryl-5-R2-1H-1,2,4-triazoles.
Compounds of this type are also formed by the condensation of N-acylimino esters of heterocyclic acids
with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine.
Keywords: amidrazones, benzothiazole, dichloropyridines, imino esters of acids, indole, 5-nitrofurans,
1,2,4-triazoles, cyclocondensation.
Hetaryl-substituted 1H-1,2,4-triazoles containing, for example, residues of 5-nitrofuran [1, 2], thiophene
[2], ∆2-imidazoline [3], pyridine [2-4], indole [5, 6], pyrazine [3], benzimidazole [7], benzothiazole [8, 9],
sym-triazine [10, 11], etc. display high antimicrobial, antistaphylococcal, hypotensive, anthelmintic, antiviral,
antispasmodic, and antihistamine activity, and also possess various pesticidal actions.
In a continuation of our investigations on the synthesis of azoles with hetaryl substituents [12-14] the
preparation is reported in the present work of 1,3,5-trisubstituted 1H-1,2,4-triazoles containing 5-nitro-2-furyl,
2-thienyl, 3-indolylmethyl, 3,5-dichloropyridyl, and 2-benzothiazolylmethyl residues. Heterocyclic systems,
combining in one molecule a 1H-1,2,4-triazole residue and the heterocycles indicated above, are of interest as
potentially biologically active substances and also as stabilizers and additives for polymeric material,
hydrocarbon fuel, and lubricants.
Convenient synthons for obtaining compounds of the 1H-1,2,4-triazole series are imino esters of
carboxylic acids and their derivatives [12, 15, 16]. In the present work the methyl imino esters of 5-nitrofuran-2-
carboxylic (1a), 3-indolylacetic (1b), and (2-benzothiazolylthio)acetic acids (1c) were used as key compounds
for obtaining trisubstituted 1H-1,2,4-triazoles. On interacting compounds 1a-c with phenyl- (2a) and
(3,5-dichloro-2-pyridyl)hydrazine (2b) in absolute methanol or in dioxane at 30-35°C N1-phenyl- and
N1-(3,5-dichloro-2-pyridyl)amidrazones of carboxylic acids 3a-e are formed in high yield (Table 1). By
condensing amidrazones 3a-e with acyl chlorides 4a-f the 1,3,5-trisubstituted 1H-1,2,4-triazoles 5a-r were
synthesized (method A). On heating (100-120°C) amidrazones 3a-e with an excess of the appropriate acyl
chloride 4a-f in an inert solvent (toluene, DMF, dioxane) for 8-10 h the yields of the target 1H-1,2,5-triazoles
5a-r amounted to 63-75% (Table 2).
__________________________________________________________________________________________
1
I. M. Gubkin Oil and Gas State University, Moscow 117917, Russia; e-mail: himeko@dol.ru.
2 Moscow A. N. Kosygin State Textile University, Moscow 117918, Russia; e-mail: office@msta.ac.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 863-871, June, 2003. Original article
submitted May 31, 2000.
736
0009-3122/03/3906-0736$25.00©2003 Plenum Publishing Corporation

TABLE 1. Characteristics of N1-Phenyl- and N1-(3,5-Dichloro-2-pyridyl)amidrazones 3a-e
Found, %
——————
Com-
Empirical
formula
Yield,
%
2
Calculated, %
mp, °С*
136-137
165-167
Rf
*
δ J
1Н NMR spectrum, , ppm. ( , Hz)
pound
C
H
N
C11H10N4O3
53.77
53.66
3.95
4.06
22.90
22.76
0.42
0.62
6.50 (2Н, br. s, NH2); 6.94 (1H, d, 3-H furan, J34 = 3.6);
7.20-7.28 (5Н, m, Ph); 7.37 (1H, d, 4-H furan, J34 = 3.6);
8.10 (1Н, br. s, NH)
84
77
3a
3b
C10H7Cl2N5O3
C16H16N4
38.11
37.97
2.30
2.21
22.04
22.15
6.42 (2Н, br. s, NH2); 6.80 (1H, d, 3-H furan, J34 = 3.5);
7.18 (1H, d, 4-H furan, J34 = 3.5); 7.78 (1H, d, 4-H pyridine,
J
46 = 1.7); 8.04 (1H, d, 6-H pyridine, J46 = 1.7);
8.18 (1Н, br. s, NH)
72.61
72.73
5.94
6.06
21.45
21.21
85-86
0.34
3.78 (2Н, s, СН2); 6.52 (2Н, br. s, NH2); 6.92–7.18 (9H, m,
78
3c
H arom.); 7.34 (1H, d, 2-H indole, J12 = 2.5);
8.04 (1Н, br. s, NH); 8.20 (1H, br. s, NH indole)
C15H14N4S2
57.23
57.32
4.52
4.46
17.96
17.83
89-90.5
170-172
0.48
0.46
3.82 (2H, s, СН2S); 6.18 (2Н, br. s, NH2);
74
85
3d
3e
7.10-7.42 (9H, m, H arom.); 8.02 (1Н, br. s, NH)
C14H11Cl2N5S2
43.67
3.02
18.04
3.46 (2H, s, СН2S); 6.26 (2Н, br. s, NH2);
43.57
2.86
18.23
7.28-7.40 (4Н, m, Н arom.); 7.79 (1H, d, 4-H pyridine, J46 = 1.8);
8.02 (1Н, br. s, NH); 8.12 (1H, d, 6-H pyridine, J46 = 1.8)
_______
* Compounds were recrystallized: 3a,e from 2-propanol–water, 3:1; 3b from ethanol; 3c from ethanol–water, 2:1; 3d
from dioxane–water, 1:2.
*2 Solvent systems: benzene–methanol, 30:1 (compounds 3a,c,e); chloroform–methanol, 40:1 (compounds 3b,d).

1
N
C
NHR
R1NHNH2
R2COCl
4a–f
2a,b
R
∆
method A
NH2
R1
R2
3a–e
N 2 1 N
NH
C
R
R
N
4
OMe
1a–c
5a–r
N
C
COR2
R1NHNH2
R2COCl
R
2a,b
4a–d,f,g
∆
OMe
6a–h
method B
CH
2
N
H
1a, 3a,b, 5a,b, 6a R =
; 1b, 3c, 5c–f, 6b,c R =
;
O N
O
2
N
1c, 3d,e, 5g–q, 6d–h R =
2b, 3b,e, 5d,e,f,l–p,r R1 =
; 2a, 3a,c,d, 5a,c,d,g–k,q R1 = Ph;
; 4a, 5a,b,e,g,l, 6a,b,e R2 = Ph;
S
SCH
2
Cl
Cl
N
4b, 5c,h, 6c R2 = 4-NO2C6H4; 4c, 5d,i,n, 6g R2 = 3,4,5-(MeO)3C6H2; 4d, 5m, 6f R2 = PhCH2; 4e, 5j,o R2 = 2-thienyl;
N
4f, 5f,k,p, 6h R2 =
; 4g, 5q,r, 6d R2 = Me
S
SCH
2
Acylation of methyl imino esters 1a-c with acid chlorides 4a-d,f,g in anhydrous ether or benzene in the
presence of triethylamine leads to the carboxylic acid methyl N-acylimino esters 6a-h in 68-80% yield
(Table 3). By condensing the N-acylimino esters 6a-h with hydrazines 2a,b (molar ratio 1:1.1) in anhydrous
dioxane or DMF at 35-40°C (3-4 h) the 1,3,5-trisubstituted 1H-1,2,4-triazoles 5a-c,e,g,i,k-n,p-r are formed in
80-90% yield (method B).
In the IR spectra of amidrazones 3a-e two absorption bands are observed at 1600-1700 cm-1. The intense
absorption maxima at 1660-1670 cm-1 correspond to the stretching vibrations of the C=N group and those at
1640-1650 cm-1 to the N–H deformation vibration in the primary amino group, which is characteristic of
amidrazones [17, 18]. The NH stretching vibrations in NH2 and N1H groups of the amidrazone fragment are
superimposed and are displayed as a broad absorption band at 3180-3320 cm-1 with a weakly expressed
separation of the maxima. Compounds 3a-e must therefore be assigned to an amidrazone structure and not to the
hydrazinoimine structure [RC(C=NH)NHNHR1] tautomeric with it [18].
In the spectra of the N-acylimino esters 6a-h the bands at 1685-1710 and 1640-1655 cm-1 correspond to
the stretching vibrations of the carbonyl and C=N groups respectively.
In the spectra of 1H-1,2,4-triazoles 5a-r the stretching vibrations of the C=N and C=C fragments of the
heteroaromatic nuclei are characterized by absorption bands of varying intensity at 1615-1630, 1575-1600,
1555-1565, and 1460-1475 cm-1. The group of bands at 1460-1475 cm-1 is characteristic of the 1,2,4-triazole
ring [19]. The presence of this ring is also confirmed by absorption bands for the stretching (1500-1510 and
1100-1125 cm-1) and deformation (950-1055 cm-1) vibrations of the 1,2,4-triazole ring [20, 21], and also by a
738

TABLE 2. Characteristics of Trisubstituted 1H-1,2,4-Triazoles 5a-r
Found, %
Yield, %
(method of
preparation)
——————
Com-
Empirical
formula
2
Calculated, %
mp, °С*
Rf
*
δ J
1Н NMR spectrum, , ppm ( , Hz)
pound
C
3
H
4
N
5
S
6
1
2
7
8
9
10
C18H12N4O3
65.17
65.06
3.52
3.61
16.98
16.87
147-148.5
0.58
7.24 (1H, d, 3-H furan, J34 = 4.0);
6.94-7.14 (10Н, m, 2Ph);
70 (A)
82 (B)
5a
7.64 (1H, d, 4-H furan, J34 = 4.0)
C17H9Cl2N5O3
50.62
50.75
2.37
2.24
8.05
8.19
152-154
(dec.)
0.44
6.90-7.02 (5H, m, Ph); 7.20 (1H, d, 3-H furan,
63 (A)
81 (B)
5b
J
34 = 3.7); 7.52 (1H, d, 4-H furan, J34 = 3.7);
7.88 (1H, d, 4-H pyridine, J46 = 1.8);
8.08 (1H, d, 6-H pyridine, J46 = 1.8)
C23H17N5O2
C26H24N4O3
70.04
69.87
4.21
4.30
17.86
17.72
137-138
158-159
0.74
0.56
3.65 (2Н, s, СН2); 6.92-7.10 (9H, m, H arom.);
7.30 (1H, d, 2-H indole, J12 = 3.1);
67 (A)
85 (B)
5c
7.48-7.58 (4H, m, H arom.); 8.20 (1H, br. s, NH indole)
70.79
70.91
5.53
5.45
12.90
12.73
3.22 (9Н, br. s, 3MеО); 3.80 (2Н, s, СН2);
6.84-7.18 (9H, m, H arom.); 7.27 (2H, s, H arom.);
7.45 (1H, d, 2-H indole, J12 = 3.7);
74 (A)
5d
8.08 (1H, br. s, NH indole)
C22H15Cl2N5
63.02
62.86
3.46
3.57
16.81
16.67
175-176.5
128-130
0.50
0.64
4.04 (2Н, s, СН2); 7.08-7.19 (9H, m, H arom.);
65 (A)
80 (B)
5e
5f
7.48 (1H, d, 2-H indole, J12 = 3.8);
7.82 (1H, d, 4-H pyridine, J46 = 1.7); 8.10 (1H, d,
6-H pyridine, J46 = 1.7); 8.20 (1H, br. s, NH indole)
C24H16Cl2N6S2
54.92
55.07
3.13
3.06
16.21
16.06
12.08
12.23
3.54 (2Н, s, СН2); 3.93 (2Н, s, СН2); 7.15-7.42 (8H, m,
68 (A)
H arom.); 7.48 (1H, d, 2-H indole, J12 = 2.5);
7.75 (1H, d, 4-H pyridine, J46 = 2.0); 8.05 (1H, d,
6-H pyridine, J46 = 2.0); 8.18 (1H, br. s, NH indole)
C22H17N4S2
115-116.5
146-147
0.58
0.63
3.68 (2H, s, СН2S); 6.88-7.04 (10H, m, 2Ph);
66 (A)
84 (B)
64 (A)
5g
5h
66.03
65.84
4.29
4.24
13.82
13.96
15.86
15.96
7.58-7.69 (4Н, m, Н arom.)
C22H16N5O2S2
59.02
3.66
15.81
14.18
3.81 (2H, s, СН2S); 6.69 (2Н, m, Н arom.);
6.84-7.01 (5H, m, Ph); 7.18 (2Н, m, Н arom.);
7.74-7.82 (4Н, m, Н arom.)
59.19
3.59
15.69
14.35
C25H22N4O3S2
61.05
61.22
4.38
4.49
11.41
11.23
12.95
13.06
134-135
0.70
3.33 (9Н, s, 3MеО); 3.95 (2H, s, СН2S);
6.92-7.05 (5H, m, Ph); 7.22 (2Н, s, Н arom.);
7.84-7.91 (4Н, m, Н arom.)
75 (A)
80 (B)
5i

TABLE 2 (continued)
1
2
3
4
5
6
7
8
9
10
C20H14N4S3
C24H17N5S4
C21H13Cl2N5S2
59.03
59.11
3.37
3.45
14.03
13.79
23.57
23.64
101-102
96-97
0.50
0.72
0.74
3.70 (2H, s, СН2S); 6.74-6.82 (5H, m, Ph);
7.54-7.83 (7Н, m, Н arom.)
72 (А)
5j
57.09
3.44
13.81
25.66
3.68 (2H, s, СН2S); 3.76 (2Н, s, СН2S);
68 (A)
90 (B)
5k
5l
57.26
3.38
13.22
25.45
6.78-6.90 (5H, m, Ph); 7.72-7.94 (8Н, m, Н arom.)
53.71
53.62
2.84
2.76
15.01
14.89
13.54
13.62
164-165.5
3.86 (2H, s, СН2S); 6.88-6.96 (5H, m, Ph);
74 (A)
3.34-7.58 (4Н, m, Н arom.); 7.77 (1H, d, 4-H pyridine,
90 (B)
J
46 = 3.0); 8.03 (1H, d, 6-H pyridine, J46 = 3.0)
C22H15Cl2N5S2
54.42
54.54
2.92
3.00
14.62
14.46
13.08
13.22
134-136
188-190
0.59
0.67
3.65 (2Н, s, СН2Рh); 3.95 (2H, s, СН2S);
6.69-6.74 (5H, m, Ph); 7.28-7.48 (4Н, m, Н arom.);
7.70 (1H, d, 4-H pyridine, J46 = 2.7);
65 (A)
83 (B)
5m
5n
7.92 (1H, d, 6-H pyridine, J46 = 2.7)
C24H19Cl2N5O3S2
51.57
51.43
3.28
3.39
12.37
12.50
11.59
11.43
3.38 (9Н, s, 3MеО); 3.80 (2H, s, СН2S); 7.08 (2H, s,
Н arom.); 7.38-7.56 (4Н, m, Н arom.); 7.88 (1H, d,
4-H pyridine, J46 = 2.7); 8.16 (1H, d, 6-H pyridine,
70 (A)
82 (B)
J
46 = 2.7)
C19H11Cl2N5S3
C23H14Cl2N6S4
47.81
47.90
2.43
2.31
14.54
14.70
20.30
20.17
156-157.5
120-122
0.50
0.77
4.04 (2H, s, СН2S); 7.28-7.47 (7Н, m, Н arom.);
7.72 (1H, d, 4-H pyridine, J46 = 1.7); 8.05 (1H, d,
6-H pyridine, J46 = 1.7)
67 (A)
5o
5p
48.25
48.17
2.35
2.44
14.81
14.66
22.20
22.34
3.84 (2H, s, СН2S); 3.95 (2Н, s, СН2S);
72 (A)
88 (B)
7.49-7.62 (8Н, m, Н arom.); 7.85 (1H, d, 4-H pyridine,
J
46 = 2.6); 8.18 (1H, d, 6-H pyridine, J46 = 2.6)
C17H14N4S2
60.22
60.35
4.22
4.14
16.45
16.57
19.11
18.93
145-146
139-140
0.80
0.64
2.38 (3Н, s, Mе); 3.94 (2H, s, СН2S);
84 (B)
87 (B)
5q
5r
6.88-7.03 (5H, m, Ph); 7.66-7.74 (4Н, m, Н arom.)
C16H11Cl2N5S2
46.92
2.81
17.01
15.85
2.65 (3Н, s, Mе); 3.87 (2H, s, СН2S);
47.06
2.70
17.16
15.68
7.52-7.66 (4Н, m, Н arom.); 7.74 (1H, d, 4-H pyridine,
J
46 = 2.1); 7.90 (1H, d, 6-H pyridine, J46 = 2.1)
_______
* Compounds were recrystallized, 5a,b,e,f,h,l,q from 2-propanol, 5c,d,g,i from 2-propanol–water, 1:1, 5j from
benzene–hexane, 5:1, 5k,m,r from 2-propanol–water, 2:1, 5n from methyl cellosolve, 5o from toluene–ethanol, 5:1, 5p
from 2-propanol–water, 4:1.
2
*
Solvent systems: benzene–methanol, 30:1 (compounds 5a,b,e,l,n,r); chloroform–methanol, 40:1 (compounds
5c,d,j,k,m,o,p); benzene–methanol, 20:1 (compounds 5f-i,q).

TABLE 3. Characteristics of Methyl N-Acyliminoesters 6a-h
Found, %
——————
Com-
Empirical
formula
Yield,
%
Calculated, %
mp, °С*
Rf*2
1Н NMR spectrum, δ, ppm (J, Hz)
pound
C
H
N
C13H10N2O5
C18H16N2O2
C18H15N3О4
C12H12N2О2S2
57.10
56.93
3.57
3.65
10.11
10.22
127-128
152-153.5
164-165
98-99
0.55
0.40
0.52
0.42
3.38 (3Н, s, MеО); 6.80 (1H, d, 3-H furan, J34 = 3.5); 6.94-7.04 (5Н, m, Ph);
7.42 (1H, d, 4-H furan, J34 = 3.5)
74
68
78
68
6a
6b
6c
6d
74.09
5.37
9.68
3.30 (3Н, s, MеО); 3.84 (2Н, s, СН2); 7.08-7.22 (9H, m, H arom.);
73.97
5.48
9.59
7.44 (1H, d, 2-H indole, J12 = 3.0); 8.14 (1H, br. s, NH indole)
63.93
64.09
4.53
4.45
12.31
12.46
3.25 (3Н, s, MеО); 4.02 (2Н, s, СН2); 7.16-7.30 (8H, m, H arom.);
7.37 (1H, d, 2-H indole, J12 = 2.7); 8.24 (1H, br. s, NH indole)
51.30
4.37
9.83
3.27 (3Н, s, MеО); 3.59 (3Н, s, MеО); 4.00 (2H, s, СН2S);
51.43
4.28
10.00
7.52-7.60 (4Н, m, Н arom.)
C17H14N2О2S2
C18H16N2О2S2
59.54
59.65
4.01
4.09
8.05
144-145.5
108-109.5
0.32
0.48
3.20 (3Н, s, MеО); 3.82 (2H, s, СН2S); 7.12-7.35 (9Н, m, Н arom.)
77
72
6e
6f
8.19
60.79
4.56
8.02
7.86
3.26 (3Н, s, MеО); 3.48 (2Н, s, СН2Рh); 3.96 (2H, s, СН2S);
6.94-7.05 (5Н, m, Ph); 7.32-7.41 (4Н, m, Н arom.)
60.67
4.49
C20H20N2О5S2
C19H15N3О2S4
55.42
55.55
4.73
4.62
6.33
Oil
0.56
0.63
3.04 (3Н, s, MеО); 3.28 (9Н, s, 3MеО); 4.10 (2H, s, СН2S);
72
71
6g
6h
(nD20 1.5874)
7.12 (2Н, s, Н arom.); 7.64-7.71 (4Н, m, Н arom.)
6.48
51.04
3.31
6.08
6.29
Oil
3.15 (3Н, s, MеО); 3.92 (2Н, s, СН2S);
51.23
3.37
4.14 (2H, s, СН2S); 7.44-7.62 (8Н, m, Н arom.)
_______
* Compounds were recrystallized: 6a,b,e from ethanol–water, 1:1; 6c from ethanol; 6d,f from acetonitrile.
*2 Solvent systems: benzene–methanol, 20:1 (compounds 6a,d,g,h); benzene–methanol, 30:1 (compounds 6b,c,e,f).

group of intense absorption bands at 1270-1290 cm-1 characteristic of the stretching vibrations of C–N bonds in
substituted 1,2,4-triazoles [21].
1
In the H NMR spectra (Tables 1-3) of amidrazones 3a,b, N-acylimino ester 6a, and 1-R1-3-(5-nitro-2-
furyl)-5-R2-1H-1,2,4-triazoles 5a,b the signals of the 3- and 4-H protons of the furan ring are observed as
doublets at 6.80-7.24 and 7.10-7.64 ppm (J34 = 3.5-4.0 Hz) respectively [22]. It should be noted that in the
spectra of 1,2,4-triazoles 5a,b the signals of these protons are displaced towards low field compared with the
spectra of amidrazones 3a,b and N-acylimino ester 6a.
In the spectra of 1,2,4-triazoles 5c-r the singlet signals at 3.65-4.10 ppm correspond to the methylene
group proton at position 3 (and also in position 5 in the spectra of compounds 5f,k,m,p). In the spectra of
compounds 3c, 5c-f, and 6b,c the signal of the 2-H proton of the pyrrole ring is displayed as a doublet at
7.30-7.48 ppm (J12 = 2.5-3.8 Hz) and in comparison with the unsubstituted indole and 3-phenylindole (6.68 and
7.03 ppm respectively [23]) is displaced towards low field. Multiplet signals at 7.36-7.82 ppm correspond to the
protons of the benzothiazole residues in the spectra of amidrazones 3d,e, N-acylimino esters 6d-h, and
1,2,4-triazoles 5f-r. The proton signals of the 3,5-dichloropyridine residues in the spectra of compounds 3b,e
and 5b,e,f,l-p,r are observed as two doublets at low field at 7.75-7.95 (4-H) and 8.04-8.16 ppm (6-H)
(J46 = 1.7-2.5 Hz).
EXPERIMENTAL
The IR spectra were obtained on a Perkin-Elmer 993 instrument in KBr disks or in nujol suspensions.
1
The H NMR spectra were recorded on a Bruker WP-250 (250 MHz) spectrometer for 10-15% solutions in
DMSO-d6, internal standard was TMS. A check on the progress of reactions and the purity of the compounds
obtained was carried out by TLC on plates with a bound layer of Al2O3 Merck LU-074, visualization was with
iodine vapor.
The initial methyl imino esters of 5-nitrofuran-2-carboxylic (1a) [24], 3-indolylacetic (1b) [25], and
(2-benzothiazolyl)thioacetic acids (1c) [26], and also (3,5-dichloro-2-pyridyl)hydrazine (2b) [27] were obtained
by known methods.
N1-Phenyl- and N1-(3,5-Dichloro-2-pyridyl)amidrazones of Carboxylic Acids (3a-e). A mixture of
methyl imino ester 1a-c (15 mmol) and hydrazine 2a,b (15 mmol) in absolute methanol (45 ml) (when making
compounds 3a,c,d) or anhydrous dioxane was stirred at 30-35°C for 4 h, cooled to 10°C, and poured into ice
water (200 ml). The solid which separated was filtered off, washed on the filter with water, dried, and
crystallized from a suitable solvent (Table 1). N1-Substituted amidrazones 3a-e were obtained.
Carboxylic Acid N-Acylimino Esters (6a-h). A solution of acyl chloride 4a-d,f,g (10 mmol) in the
corresponding solvent (25 ml) was added dropwise to a stirred mixture of methyl imino ester 1a-c (10 mmol)
and dry triethylamine (1.01 g, 10 mmol) in anhydrous ether (10 ml) (when making compounds 6a-c) or
anhydrous benzene at 0°C. The reaction mixture was stirred at 30-35°C for 4-6 h, cooled to 20°C, and poured
into 3% NaHCO3 solution (70 ml). The organic layer was separated, washed with water (2 × 20 ml), dried over
Na2SO4, and evaporated to dryness at reduced pressure. The residue was either crystallized from a suitable
solvent (Table 3), or chromatographed on a column (40 × 4.5 cm) of Al2O3 (when obtaining compounds 6g,h),
eluting with benzene–2-propanol, 10:1. After removing the solvent N-acylimino esters 6g,h were obtained as
viscous dark yellow uncrystallizing oils.
1,3,5-Trisubstituted 1H-1,2,4-Triazoles (5a-r). A. A mixture of amidrazone 3a-e (4 mmol) and acyl
chloride 4a-f (10 mmol) in anhydrous solvent (30 ml) (toluene when making 5a,d,g,i-k; dioxane when making
5c,h; DMF when making 5b,e,f,l-r) was stirred at 110-120°C for 10 h. The solvent was removed at reduced
pressure, and the residue treated with 5% NaOH solution (30 ml). The isolated solid was filtered off, washed on
the filter with water, dried, and crystallized from a suitable solvent (Table 2). 1H-1,2,4-Triazoles 5a-r were
obtained.
742

B. A mixture of N-acylimino ester 6a-h (10 mmol) and hydrazine 2a,b (11 mmol) in anhydrous dioxane
(45 ml) or anhydrous DMF (when making 5b,e,l-n,p,r) was stirred at 35-40°C for 4 h, then evaporated to
dryness at reduced pressure. The residue was crystallized from a suitable solvent (Table 2) and 1H-1,2,4-
triazoles 5a-c,e,g,i,k-n,p,r were obtained.
The work was carried out with the financial support of the MO of the Russian Federation.
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